Milner J
Department of Biology, University of York, UK.
Pathol Biol (Paris). 1997 Dec;45(10):797-803.
The tumour suppressor p53 plays a crucial role in the cellular response to DNA damage. The p53 protein is able both to detect sites of DNA damage and to interact with DNA in a sequence-specific manner and function in the regulation of target gene expression. These two properties map to discrete functional domains of the protein, the C-terminus and the central core domain respectively. They are essential for integration of a normal cellular response to DNA damage, with initiation of either G1 cell cycle arrest or apoptosis. This review considers the domain structure of p53 in relation to the protein's various functions, together with the importance of tertiary structure and conformational flexibility. The precise regulation of p53 function remains to be established, although the protein is known to be phosphorylated/de-phosphorylated by a number of specific protein kinases/phosphatases. A recent discovery indicates that p53 may be activated by autoproteolysis and that proteolytic cleavage is induced by direct interaction with sites of DNA damage. This process is reminiscent of the bacterial Lex A system and would provide one mechanism for activation of p53 in response to cellular DNA damage.
肿瘤抑制因子p53在细胞对DNA损伤的反应中起关键作用。p53蛋白既能检测DNA损伤位点，又能以序列特异性方式与DNA相互作用，并在靶基因表达调控中发挥作用。这两种特性分别映射到该蛋白的离散功能结构域，即C末端和中央核心结构域。它们对于整合细胞对DNA损伤的正常反应以及启动G1细胞周期阻滞或凋亡至关重要。本综述探讨了p53的结构域结构与其各种功能的关系，以及三级结构和构象灵活性的重要性。尽管已知p53可被多种特定蛋白激酶/磷酸酶磷酸化/去磷酸化，但其功能的确切调控仍有待确定。最近的一项发现表明，p53可能通过自蛋白水解被激活，并且蛋白水解切割是由与DNA损伤位点的直接相互作用诱导的。这一过程让人联想到细菌Lex A系统，并且将为p53响应细胞DNA损伤而被激活提供一种机制。
